{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:35:59Z","timestamp":1792802159617,"version":"4.5.0"},"reference-count":26,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,12]],"date-time":"2023-01-12T00:00:00Z","timestamp":1673481600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Vifor"},{"name":"Boehringer Ingelheim"},{"name":"Societa Prodotti Antibiotici"},{"name":"AstraZeneca"},{"name":"Roche"},{"name":"Servier"},{"name":"Novartis"},{"name":"GENESIS"},{"name":"Cytokinetics"},{"name":"Medtronic"},{"name":"Boston Scientific"},{"name":"PHARMACOSMOS"},{"name":"Merck"},{"name":"Bayer"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Endothelial dysfunction (ED) causes worse prognoses in heart failure (HF) patients treated with cardiac resynchronization therapy (CRTd). ED triggers the downregulation of microRNA-130 (miR-130a-5p), which targets endothelin-1 (ET-1). Thus, we evaluated ED and the response to CRTd by assessing miR-130a-5p and ET-1 serum levels. We designed a prospective multi-center study with a 1-year follow-up to evaluate ED, ET-1, and miR-130a-5p in CRTd patients with ED (ED-CRTd) vs. patients without ED (NED-CRTd). Clinical outcomes were CRTd response, HF hospitalization, cardiac death, and all-cause death. At 1-year follow-up, NED-CRTd (n = 541) vs. ED-CRTd (n = 326) patients showed better clinical statuses, lower serum values of B type natriuretic peptide (BNP: 266.25 \u00b1 10.8 vs. 297.43 \u00b1 16.22 pg\/mL; p &lt; 0.05) and ET-1 (4.57 \u00b1 0.17 vs. 5.41 \u00b1 0.24 pmol\/L; p &lt; 0.05), and higher values of miR-130a-5p (0.51 \u00b1 0.029 vs. 0.41 \u00b1 0.034 A.U; p &lt; 0.05). Compared with NED-CRTd patients, ED-CRTd patients were less likely to be CRTd responders (189 (58%) vs. 380 (70.2%); p &lt; 0.05) and had higher rates of HF hospitalization (115 (35.3%) vs. 154 (28.5%); p &lt; 0.05) and cardiac deaths (30 (9.2%) vs. 21 (3.9%); p &lt; 0.05). Higher miR-130a-5p levels (HR 1.490, CI 95% [1.014\u20132.188]) significantly predicted CRTd response; the presence of hypertension (HR 0.818, CI 95% [0.669\u20130.999]), and displaying higher levels of ET-1 (HR 0.859, CI 98% [0.839\u20130.979]), lymphocytes (HR 0.820, CI 95% [0.758\u20130.987]), LVEF (HR 0.876, CI 95% [0.760\u20130.992]), and ED (HR 0.751, CI 95% [0.624\u20130.905]) predicted CRTd non-response. Higher serum miR-130a-5p levels (HR 0.332, CI 95% [0.347\u20130.804]) and use of ARNI (HR 0.319, CI 95% [0.310\u20130.572]) predicted lower risk of HF hospitalization, whereas hypertension (HR 1.818, CI 95% [1.720\u20132.907]), higher BNP levels (HR 1.210, CI 95% [1.000\u20131.401]), and presence of ED (HR 1.905, CI 95% [1.238\u20132.241]) predicted a higher risk of HF hospitalization. Hence, serum miR-130a-5p could identify different stages of ED and independently predict CRTd response, therefore representing a novel prognostic HF biomarker.<\/jats:p>","DOI":"10.3390\/ijms24021510","type":"journal-article","created":{"date-parts":[[2023,1,12]],"date-time":"2023-01-12T06:25:57Z","timestamp":1673504757000},"page":"1510","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Endothelial Dysfunction Drives CRTd Outcome at 1-Year Follow-Up: A Novel Role as Biomarker for miR-130a-5p"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5099-3790","authenticated-orcid":false,"given":"Celestino","family":"Sardu","sequence":"first","affiliation":[{"name":"Department of Advanced Medical and Surgical Sciences, University of Campania \u201cLuigi Vanvitelli\u201d, 80126 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7231-375X","authenticated-orcid":false,"given":"Gaetano","family":"Santulli","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiology, Albert Einstein College of Medicine, New York, NY 10461, USA"},{"name":"Department of Advanced Biomedical Sciences, \u201cFederico II\u201d University, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluigi","family":"Savarese","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiology, Karolinska Institutet, Heart, Vascular and Neuro Theme, Karolinska University Hospital, 17177 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9813-5955","authenticated-orcid":false,"given":"Maria Consiglia","family":"Trotta","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, 80126 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cosimo","family":"Sacra","sequence":"additional","affiliation":[{"name":"Cardiovascular and Arrhythmias Department \u201cGemelli Molise\u201d, 86100 Campobasso, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Santamaria","sequence":"additional","affiliation":[{"name":"Cardiovascular and Arrhythmias Department \u201cGemelli Molise\u201d, 86100 Campobasso, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Volpicelli","sequence":"additional","affiliation":[{"name":"Cardiovascular Diseases and Electrophysiology Unit, \u201cS. Maria della Piet\u00e0 Hospital\u201d, 80035 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Ruocco","sequence":"additional","affiliation":[{"name":"Cardiovascular Diseases and Electrophysiology Unit, \u201cCardarelli Hospital\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ciro","family":"Mauro","sequence":"additional","affiliation":[{"name":"Cardiovascular Diseases and Electrophysiology Unit, \u201cCardarelli Hospital\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6609-2708","authenticated-orcid":false,"given":"Giuseppe","family":"Signoriello","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, 80126 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenza","family":"Marfella","sequence":"additional","affiliation":[{"name":"Department of Advanced Medical and Surgical Sciences, University of Campania \u201cLuigi Vanvitelli\u201d, 80126 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6899-0595","authenticated-orcid":false,"given":"Michele","family":"D\u2019Amico","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, 80126 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3960-9270","authenticated-orcid":false,"given":"Raffaele","family":"Marfella","sequence":"additional","affiliation":[{"name":"Department of Advanced Medical and Surgical Sciences, University of Campania \u201cLuigi Vanvitelli\u201d, 80126 Naples, Italy"},{"name":"\u201cMediterranea Cardiocentro\u201d, 80122 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Paolisso","sequence":"additional","affiliation":[{"name":"Department of Advanced Medical and Surgical Sciences, University of Campania \u201cLuigi Vanvitelli\u201d, 80126 Naples, Italy"},{"name":"\u201cMediterranea Cardiocentro\u201d, 80122 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.cardfail.2013.05.001","article-title":"Endothelial dysfunction is a marker of systemic response to the cardiac resynchronization therapy in heart failure","volume":"19","author":"Santini","year":"2013","journal-title":"J. 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